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Biomedical subjects

M Villalobos

Publications and source records attributed to M Villalobos.

At least 37 records · Page 2Linked to original sources

Prostaglandin F2a (PGF2a): an inadequate marker of the vitality of wounds?

We have studied the viability of PGF2a as a vitality marker in skin wounds. Incised vital skin wounds and homolateral control pieces of skin were obtained from 20 autopsies performed at the Institute of Legal Medicine of Coimbra University (Portugal). We have also studied 10 fresh skin samples from the Department of Dermatology of the University Hospital (Granada). Our results show that PGF2a is not suitable for the diagnosis of the vitality of wounds because of its irregular behaviour.

Biomarkers↗

Analysis of risk of death from differentiated thyroid cancer.

The records of 231 patients with differentiated thyroid cancer, treated at the University Hospital of Granada between 1972 and 1986, were reviewed to determine which factors were associated with a favourable response and prolonged survival. Radical surgery was the initial treatment in the large majority of the patients. During the postoperative period, 174 patients received 131I therapy and 12 patients were treated by external irradiation. All of them received hormone replacement therapy. Median follow up was over 5 years. Kaplan-Meier actuarial overall survival (S) and disease-free survival (DSF) at 10 years were used as end points for analysis. Survival and freedom from relapse at this time were 0.93 +/- 0.02 and 0.63 +/- 0.06, respectively. No flattening of the relapse curve was observed during the period of follow-up. Univariate analysis showed that the prognosis was significantly influenced by age, sex (papillary cancer only), histological type of tumour, clinical-pathological stage of disease and cervical lymph node status (entire group and papillary cancer). Using Cox's regression model, two groups of patients with low and moderate risk of death and moderate and high risk of recurrence could be identified.

Actuarial Analysis↗

Initial radiation-induced DNA damage in human tumour cell lines: a correlation with intrinsic cellular radiosensitivity.

The role of the initial DNA double-strand breaks (dsb) as a determinant of cellular radiosensitivity was studied in human breast and bladder cancer cell lines. Cell survival was measured by monolayer colony-forming assay as appropriate and differences in radiosensitivity were seen (alpha-values ranged from 0.12 to 0.54). After pulsed-field gel electrophoresis (PFGE) the initial slopes of dose-response curves were biphasic with a flattening of the curves above 30 Gy. When the frequency of DNA dsb induction was assessed using a mathematical model based on the DNA fragment size distribution into the gel lane, we found a statistically significant relationship between the number of DNA dsb induced and the corresponding alpha-values and fraction surviving after 2Gy (P = 0.0049 and P = 0.0031 respectively). These results support the view that initial damage is a major determinant of cell radiosensitivity.

Breast Neoplasms↗

Evaluation of the growth rate of MCF-7 breast cancer multicellular spheroids using three mathematical models.

Growth data on 60 multicellular spheroids of MCF-7 human breast cancer cells were fitted, on an individual basis, by the Gompertz, Bertalanffy and logistic equations. MCF-7 spheroids, initiated and grown in medium containing oestrogens, exhibited a growth rate that decreased continuously as spheroid size increased. Plots of spheroid volume v. time generated sigmoid curves that showed an early portion with an approximately exponential volume increase; a middle region or retardation phase characterized by a continuously decreasing growth rate; and, finally, a late segment or plateau phase approaching zero growth rate, that permitted an estimate of the maximum spheroid size (Vmax). Growth curves generated by MCF-7 spheroids under different experimental conditions (hormones, drugs and radiation exposures) can be compared after normalization. Linearized forms of the fitted Gompertz curves provided a convenient way to express differences in growth rate.

Breast Neoplasms↗

MCF-7 breast cancer cells grown as multicellular spheroids in vitro: effect of 17 beta-estradiol.

To obtain multicellular spheroids from MCF-7 human breast cancer cells we adhered to the following procedure: (a) limiting the adherence of cell to the substratum; (b) seeding more than the minimum number of cells; (c) guaranteeing the presence of estrogens in the culture medium. Charcoal-dextran (CD)-treated sera seemed to inhibit spheroid formation. A reduction in the concentration of CD-human sera (from 10% to 5%) added to phenol-red-free medium facilitated progress from cellular aggregates to multicellular spheroids. Once the spheroids became initiated, size increased at a rate that showed a good fit to a Gompertzian equation (A = 0.368 +/- 0.067 alpha = 0.065 +/- 0.013, r range = 0.890-0.989). Three different patterns of spheroid morphology and proliferative kinetic were defined: (a) spheroids with diameter less than 200 microns had a constant pattern of heterogeneity in the distribution of 3H-TdR-labelled cells and in the expression of estrogen receptors; (b) spheroids 250 to 700 microns in diameter showed a decrease in the proportion of 3H-TdR-labelled cells accompanying inward progression (50% in the outer shell, less than 10% in a cell layer located at a depth of 150 microns) while, at a depth of 170 microns, of signs of concurrent cellular degeneration and death were apparent; and (c) spheroids with a diameter of greater than 750 microns showed a crust of viable cells uniformly labelled with thymidine without impairment of the proportion of labelled cells when progressing inward from the spheroid crust. The larger the spheroid volume, the lower its growth fraction and the longer its volume doubling time. The hormone-dependence of MCF-7 cells in forming multicellular spheroids represents a unique experimental model for assessing estrogen action on cell organization and proliferation.

Breast Neoplasms↗

Differential response to aminergic stimuli and biological behavior of growth hormone secreting pituitary adenomas.

Growth hormone (GH) serum levels in response to the administration of aminergic drugs and thyroliberine (TRH) were determined in a group of 34 acromegalics. Administration of bromocriptine (10 mg single oral dose) was followed by a decrease in GH below 60% control values in 35% of the cases. Administration of diazepam (10 mg single oral dose) to those cases not responding to bromocriptine induced a decrease in GH in 58% of the cases and an increase in GH in 42%. Administration of cyproheptadine (24 mg/day for one month) to those cases not responding to bromocriptine or with increased GH after the administration of diazepam, decreased GH in 75%, while increased GH in 25% of the cases. TRH 200 micrograms single I.V. dose induced increase of 128% GH basal level in 65% of cases (TRH positive) which correlated with more benign clinical course, decreased GH levels in response to bromocriptine, increased PRL levels, PRL-GH mixed secreting adenomas in immunohistochemistry studies, presence of granulated cells in electron microscopy studies and normalization of GH in the majority of surgically treated cases. By contrast, TRH negative cells correlated with aggressive tumor growth, lack of response to bromocriptine, normal PRL levels, pure GH secreting adenomas by immunohistochemistry, poorly granulated cells and lack of response to surgical treatment. Results suggest that there is more than one type of acromegaly that might be distinguished by the aminergic control on GH secretion.

Acromegaly↗

[Proliferation kinetics of MCF-7 cell cultures. I. Relative influence of estrogens and antiestrogens on the growth of the cell population].

The cellular hormone dependent cell line MCF-7 is a tumoral model of mammary cancer the growth kinetics of which operating under the influence of varied and opposed hormonal factors (estrogens and antiestrogens at precise concentration levels) has provided the means of knowing the action mechanisms of such agents. In this study, carried out with cultured MCF-7 cells under well defined experimental conditions, it has been shown that: 1) antiestrogens (OH-TAM) seem to be opposed to the growing process of the cellular population the elements of which, under the influence of OH-TAM, double the value of the parameter TD (Doubling Time); 2) estrogens (17-beta-E2) cancel out this effect and promote the growth of MCF-7 cells whether OH-TAM is previously or simultaneously added to the culture medium; 3) the observation of this estrogenic action needs accurate experimental conditions without which the effect may not be seen.

Cell Division↗

[Proliferation kinetics of MCF-7 cell cultures. II. Synchronization and cell recruitment induced by hormones].

The culture of MCF-7 cells in well known experimental conditions and the analysis of the cellular uptake of 3HTdR under the influence of estrogens (17-beta-E2) and antiestrogens (OH-TAM) at precise concentration levels (10(-6)/10(-9) M) have made possible the study of the growing kinetic process of the cellular cultured population and the determination of the action of such hormonal preparations on the same process. The main findings are as follows: the growing rate of the cultured cells appears to slow down in presence of OH-TAM; the reason for this slowing growth seems to be the "blockade" of the cultured cells in the last part of G1 phase, a phenomenon that has proved to be dose-dependent; by the stimulating effect of the 17-beta-E2, the MCF-7 cells, synchronized in G1, progress simultaneously in their vital cycle during, at least, three divisory cycles; and this "recruitment" effect seems to be characteristic of the estrogen since the synchronization process fades or disappears when the 17-beta-E2 is absent from the culture medium.

Cell Division↗

Low frequency hereditary deafness in man with childhood onset.

A large kindred of hereditary deaf affected with a progressive sensorineural loss that begins during childhood with the low audiologic frequencies is described. Deafness progresses slowly through adolescence, when losses of up to 70 decibels are often detected. Affected adults present profound losses at all frequencies. Genetically, this deafness is transmitted as a simple, dominant, and autosomal mutation. No associated abnormalities have been detected in studies involving medical examinations, care histories, quantitation of several blood serum components, electrocardiograms, electrophoretograms, and karyotypes.

Adolescent↗